Marchetti B, Labrie F
MRC Group in Molecular Endocrinology, Laval University Medical Center, Québec, Canada.
J Steroid Biochem. 1988 Jun;29(6):691-8. doi: 10.1016/0022-4731(88)90170-7.
The effect of daily treatment with the pure antiandrogen Flutamide has been studied either alone or in combination with the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide (LHRH-A), on testicular and prostatic functions in adult male rats. Treatment for 10 days with Flutamide (5 mg/rat, twice daily) caused a marked stimulation of plasma testosterone (T) associated with a significant increase in plasma gonadotropin concentrations and inhibited plasma PRL levels. Testicular weight is not changed following antiandrogen administration but testicular LH/hCG receptor levels are markedly decreased with no change in FSH receptor levels. Moreover, Flutamide treatment alone produces an important inhibition of ventral prostate and seminal vesicle weights associated with a significant decrease in prostatic beta-adrenergic receptor levels but no change is observed in specific ornithine decarboxylase (ODC) activity. Daily LHRH-A treatment at the dose of 1 microgram/day for 10 days decreases plasma T to levels comparable to those found in orchiectomized men (0.30 +/- 0.5 ng/ml). This effect is associated with an almost complete loss of testicular LH/hCG receptors, a decrease in testicular weight, a significant increase in plasma gonadotropins and a marked inhibition of plasma PRL concentration. A relatively smaller inhibition of ventral prostate and seminal vesicle weights follows treatment with the LHRH agonist alone, this effect being accompanied by a significant reduction in beta-adrenergic receptor concentration but no change in prostatic ODC activity. Combination of the two drugs, however, caused a potent inhibitory effect on both ventral prostate and seminal vesicle weight to values similar to those found in castrated rats. The prostatic weight loss is accompanied by a marked fall in ODC activity and in the concentration of beta-adrenergic receptors. The present data clearly show that combined treatment with an LHRH agonist and a pure antiandrogen is highly effective in inhibiting, not only prostatic growth, but also two androgen-sensitive parameters of prostatic activity.
已对成年雄性大鼠单独使用纯抗雄激素氟他胺或与促性腺激素释放激素（LHRH）激动剂[D-色氨酸6，去甘氨酰胺（10）]LHRH乙酰胺（LHRH-A）联合每日治疗对睾丸和前列腺功能的影响进行了研究。用氟他胺（5毫克/大鼠，每日两次）治疗10天，导致血浆睾酮（T）显著升高，同时血浆促性腺激素浓度显著增加，并抑制血浆催乳素水平。给予抗雄激素后，睾丸重量未改变，但睾丸LH/hCG受体水平显著降低，而FSH受体水平无变化。此外，单独使用氟他胺治疗可显著抑制腹侧前列腺和精囊重量，同时前列腺β-肾上腺素能受体水平显著降低，但鸟氨酸脱羧酶（ODC）的特异性活性未见变化。每日以1微克/天的剂量给予LHRH-A治疗10天，可使血浆T降至与去势男性相当的水平（0.30±0.5纳克/毫升）。这种作用伴随着睾丸LH/hCG受体几乎完全丧失、睾丸重量减轻、血浆促性腺激素显著增加以及血浆催乳素浓度显著抑制。单独使用LHRH激动剂治疗后，对腹侧前列腺和精囊重量的抑制作用相对较小，这种作用伴随着β-肾上腺素能受体浓度显著降低，但前列腺ODC活性无变化。然而，两种药物联合使用对腹侧前列腺和精囊重量均产生了强大的抑制作用，使其值与去势大鼠相似。前列腺重量减轻伴随着ODC活性和β-肾上腺素能受体浓度显著下降。目前的数据清楚地表明，LHRH激动剂与纯抗雄激素联合治疗不仅对前列腺生长有高效抑制作用，而且对前列腺活性的两个雄激素敏感参数也有抑制作用。
